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Elife. 2019 May 2;8. pii: e45051. doi: 10.7554/eLife.45051. [Epub ahead of print]

The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity.

Author information

1
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
2
MRC Functional Genomics Unit, University of Oxford, Oxford, United Kingdom.
3
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
4
British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
5
Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

Abstract

To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes. How an effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly understood. Here we show that Cerox1, an unusually abundant cytoplasmic long noncoding RNA (lncRNA), modulates the levels of mitochondrial complex I subunit transcripts in a manner that requires binding to microRNA-488-3p. Increased abundance of Cerox1 cooperatively elevates complex I subunit protein abundance and enzymatic activity, decreases reactive oxygen species production, and protects against the complex I inhibitor rotenone. Cerox1 function is conserved across placental mammals: human and mouse orthologues effectively modulate complex I enzymatic activity in mouse and human cells, respectively. Cerox1 is the first lncRNA demonstrated, to our knowledge, to regulate mitochondrial oxidative phosphorylation and, with miR-488-3p, represent novel targets for the modulation of complex I activity.

KEYWORDS:

biochemistry; chemical biology; genetics; genomics; human; mouse

PMID:
31045494
DOI:
10.7554/eLife.45051
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Conflict of interest statement

TS, KR, WH, OB, SR, JT, NL, LH, RC, SC, AF, JW, NM, AM The other authors declare that no competing interests exist. CP Chris P Ponting, Reviewing editor, eLife.

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